The principal focus of this subproject is to examine the level and sequence of expression of 8 regulators of bone metabolism during bone regeneration under a polytetrafluorethylene membrane in the rhesus monkey and the rat. We hypothesize that the levels of growth factors secreted locally during neo-osteogenesis specifically PDGF, IL-4, TGFbeta, IGF-1 and delta12-PGJ2, ultimately determines the mass and structural properties of regenerated bone. We will determine the level and kinetics of expression of these growth factors during the ridge regeneration in the monkey and rat. Biopsy tissue samples will be collected at specific time points and analyzed for these growth factors. The levels of mediators will be correlated to the bone mass, mineral content, rate of bone formation, rate of mineralization and selected structural properties as determined by companion subprojects. Tissues will also be analyzed from underexposed or "failing" membranes for analyses of catabolic bone mediators PGE2, IL-1beta and TNFalpha and compared to time-matched, non- exposed samples. Using the rat mandible critical size defect model, we will elucidate the role of delta12-PGJ2 in regeneration by blocking synthesis using indomethacin and by supplementation with a delta12-PGJ2- containing carboxymethylcellulose gel.